Dermal and Transdermal Cryogenic Microprobe Systems

ABSTRACT

Medical devices, systems, and methods optionally treat dermatological and/or cosmetic defects, and/or a wide range of additional target tissues. Embodiments apply cooling with at least one small, tissue-penetrating probe, the probe often comprising a needle having a size suitable for inserting through an exposed surface of the skin of a patient without leaving a visible scar. Treatment may be applied along most or all of the insertable length of an elongate needle, optionally by introducing cryogenic cooling fluid into the needle lumen through a small, tightly-toleranced lumen of a fused silica fluid supply tube, with the supply tube lumen often metering the cooling fluid. Treatment temperature and/or time control may be enhanced using a simple pressure relief valve coupled to the needle lumen via a limited total exhaust volume space.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a Continuation of U.S. Ser. No. 14/982,728filed Dec. 29, 2015 (Allowed); which is a Continuation of U.S. Ser. No.11/614,887 filed Dec. 21, 2006 (now U.S. Pat. No. 9,254,162); the fulldisclosures which are incorporated herein by reference in their entiretyfor all purposes.

BACKGROUND OF THE INVENTION

The present invention is generally directed to medical devices, systems,and methods, particularly for cooling-induced remodeling of tissues.Embodiments of the invention include devices, systems, and methods forapplying cryogenic cooling to dermatological tissues so as toselectively remodel one or more target tissues along and/or below anexposed surface of the skin. Embodiments may be employed for a varietyof cosmetic conditions, optionally by inhibiting undesirable and/orunsightly effects on the skin (such as lines, wrinkles, or cellulitedimples) or on other surrounding tissue. The remodeling of the targettissue may achieve a desired change in its behavior or composition.

The desire to reshape various features of the human body to eithercorrect a deformity or merely to enhance one's appearance is common.This is evidenced by the growing volume of cosmetic surgery proceduresthat are performed annually.

Many procedures are intended to change the surface appearance of theskin by reducing lines and wrinkles. Some of these procedures involveinjecting fillers or stimulating collagen production. More recently,pharmacologically based therapies for wrinkle alleviation and othercosmetic applications have gained in popularity.

Botulinum toxin type A (BOTOX®) is an example of a pharmacologicallybased therapy used for cosmetic applications. It is typically injectedinto the facial muscles to block muscle contraction, resulting intemporary innervation or paralysis of the muscle. Once the muscle isdisabled, the movement contributing to the formation of the undesirablewrinkle is temporarily eliminated. Another example of pharmaceuticalcosmetic treatment is mesotherapy, where a cocktail of homeopathicmedication, vitamins, and/or drugs approved for other indications isinjected into the skin to deliver healing or corrective treatment to aspecific area of the body. Various cocktails are intended to effect bodysculpting and cellulite reduction by dissolving adipose tissue, or skinresurfacing via collagen enhancement. Development ofnon-pharmacologically based cosmetic treatments also continues. Forexample, endermology is a mechanical based therapy that utilizes vacuumsuction to stretch or loosen fibrous connective tissues which areimplicated in the dimpled appearance of cellulite.

While BOTOX® and/or mesotherapies may temporarily reduce lines andwrinkles, reduce fat, or provide other cosmetic benefits they are notwithout their drawbacks, particularly the dangers associated withinjection of a known toxic substance into a patient, the potentialdangers of injecting unknown and/or untested cocktails, and the like.Additionally, while the effects of endermology are not known to bepotentially dangerous, they are brief and only mildly effective.

In light of the above, it would be desirable to provide improved medicaldevices, systems, and methods, particularly for treatment of wrinkles,fat, cellulite, and other cosmetic defects. It would be particularlydesirable if these new techniques provided an alternative visualappearance improvement mechanism which could replace and/or complimentknown bioactive and other cosmetic therapies, ideally allowing patientsto decrease or eliminate the injection of toxins and harmful cocktailswhile providing similar or improved cosmetic results. It would also bedesirable if such techniques were performed percutaneously using onlylocal or no anesthetic with minimal or no cutting of the skin, no needfor suturing or other closure methods, no extensive bandaging, andlimited or no bruising or other factors contributing to extendedrecovery or patient “down time”. It would further be desirable toprovide new devices, systems, and methods for treatment of othercosmetic and/or dermatological conditions (and potentially other targettissues), particularly where the treatments may be provided with greateraccuracy and control, less collateral tissue injury and/or pain, andgreater ease of use.

BRIEF SUMMARY OF THE INVENTION

The present invention generally provides improved medical devices,systems, and methods. Embodiments may be particularly well suited forthe treatment of dermatological and/or cosmetic defects, and alternativeembodiments may be configured for treatment of a wide range of targettissues. Some embodiments of the present invention apply cooling with atleast one small, tissue-penetrating probe, the probe often comprising aneedle having a size suitable for inserting through an exposed surfaceof the skin of a patient without leaving a visible scar. The cooling mayremodel one or more target tissue so as to effect a desired change in acomposition of the target tissue and/or a change in its behavior.Treatment may be applied along most or all of the insertable length ofan elongate needle, optionally by introducing cryogenic cooling fluidinto the needle lumen through a small, tightly-toleranced lumen of afused silica fluid supply tube, with the supply tube lumen oftenmetering the cooling fluid. Treatment temperature and/or time controlmay be enhanced using a simple pressure relief valve coupled to theneedle lumen with a limited total exhaust volume space.

In a first aspect, the invention provides a system for treating a targettissue of a patient. The system comprises a needle having a proximalend, a distal end, and a lumen therebetween, with the needle having a 16gauge or smaller needle size. A cooling fluid supply lumen extendsdistally within the needle, and a cooling fluid source is coupleable tothe supply lumen to direct cooling fluid flow into the needle lumen sothat liquid from the cooling flow vaporizes within the target tissuewhen the needle extends into the target tissue.

In many cases, the needle will have a 25 gauge or smaller needle sizeand a tip for penetrating a skin surface. Exemplary embodiments comprise30 gauge or smaller needles. The needles will often comprise metallicstructures, typically comprising stainless steel hypotube.

The supply lumen may reside in a non-metallic supply tube, with theexemplary supply tube comprising fused silica. A polymer may be disposedover the fused silica, with an outer diameter of the polymer preferablybeing less than 800 μm, and ideally less than 200 μm. The supply tubegenerally extends in cantilever distally into the needle lumen so thatit will be advantageous to employs supply tubes of fused silica or othermaterials with sufficient stiffness to inhibit flow induced buckling ofthe supply tube within the needle lumen. The exemplary fused silicasupply tubes are particularly well suited for use within high aspectratio needles, such as those having a ratio between an insertable lengthof the needle to an outer size of the needle of more than 20, the aspectratio optionally being at least 100, although shorter needles may alsobe used. In many embodiments, the supply lumen has an inner diameter ofless than 100 μm, often being less than 50 μm, and preferably being lessthan 35 μm, and the exemplary non-metallic supply tubes provide goodsystem durability in the demanding cryogenic environment within theneedle despite their very small size.

A handle may support the needle, the supply lumen, and the fluid sourcefor manual manipulation and positioning of the system during treatment.A pressure relief valve will often be in fluid communication with theneedle lumen so as to control a pressure of the vaporizing cooling flowwithin the needle. This can effectively provide cooling of the targettissue to a treatment temperature within a desired treatment temperaturerange. In the exemplary embodiment, nitrous oxide cooling liquid ismaintained at about room temperature in a sealed canister prior to use,with the canister being pierced to initiate cooling flow into the needlelumen. The vaporizing liquid drives the cooling fluid through the supplytube and into the needle so that the needle lumen includes a mixture ofliquid and gas. The flow can be metered primarily by a flow resistanceof the supply lumen, the flow optionally being substantially entirelymetered by the flow resistance, particularly when using the exemplarysmall lumen diameter fused silica supply tubes (as they can have quiteuniform lumen diameters). In some embodiments, the flow may not beactively modulated between the fluid source and the needle lumen duringcooling.

It will often be advantageous to limit a size of the cooling fluidexhaust pathway to improve treatment temperature and time control. Insome embodiments, the pressure relief valve comprises a biasing springmechanically urging a valve member against a valve seat so as tomaintain pressure of the needle lumen within a desired pressure range.An exhaust volume may be defined along the cooling fluid path betweenthe supply lumen and the valve seat, with the biasing spring typicallybeing disposed outside the exhaust volume to minimize the size of theexhaust volume and. The exhaust volume is preferably less than about0.05 in³, typically being less than 0.01 in³, ideally being less than0.005 in³.

It will also be beneficial to limit the effect of liquid cooling fluiddisposed along the intake pathway when the valve is shut off. Ingeneral, a supply valve will be disposed between the supply lumen andthe fluid source. The cooling fluid supply volume along the coolingfluid path between the needle lumen and the supply valve may be ventedby the supply valve. More specifically, the valve may have a firstconfiguration and a second configuration, the valve in the firstconfiguration providing fluid communication between the fluid source andthe supply volume, the valve in the second configuration inhibiting thecooling flow and venting the supply volume so as to limit cooling fluidvaporization within the needle lumen after the valve moves from thefirst configuration to the second configuration.

At least one distally oriented skin engaging surface will often beprovided. For example, a handpiece body may support the needle, and theat least one skin engaging surface may be supported by the handpiecebody so as to engage the skin surface before and/or during cooling ofthe target tissue. In some embodiments, an insertable length of theneedle between the distal end of the needle and the at least one skinengaging surface may be selectably alterable, for example, by providinga plurality of spacer bodies, the spacer bodies having differingthicknesses. The user can select an effective needle length by mountingan appropriate spacer to the handpiece and/or needle. Optionally, theskin engaging surface may be extendable distally beyond the needle toavoid unintentional needle sticks, apply cooling to the skin adjacentthe needle insertion location, or pressure to dull any needle insertionpain, or the like. Hence, an articulatable support may couple the skinengaging surface to the needle so the skin engaging surface applies apain dulling pressure to the skin before and/or during skin penetrationby the needle. To cool the skin engaging surface, it may be thermallycoupled to a skin cooling chamber, wherein a skin cooling port directscooling fluid from the fluid source into the skin cooling chamber. Wherethe skin surface is cooled to a more moderate temperature than thetarget tissue engaged by the needle, the skin cooling chamber can have ahigher operating pressure than the needle lumen. For example, the skinengaging surface may be configured to cool the skin to a more moderate,safe temperature (often being above −15° C., optionally being above −10°C., in some cases being above 0° C.) to inhibit inflammation, while theneedle is configured to more significantly cool the target tissue(typically to significantly below 0° C., and in many cases being below−15° C.) to induce necrosis.

Cooling rates may be tailored within a wide range to promote desiredtherapeutic results. For example, when the flow is initiated, an outersurface of the needle engaging the target tissue may cool at a rate ofmore than about 25° C./sec (optionally being more than about 40° C./sec)so as to promote intracellular ice formation and necrosis of the targettissue. In such embodiments, an array of needles can be coupled to thefluid source can have similar cooling rates to promote intracellular iceformation and necrosis of the target tissue between the needles.Alternatively, lower engaged tissue cooling rates may be used to helppromote osmotic effects that inhibit intracellular ice formation andassociated necrosis. A variety of more sophisticated embodiments maymake use of multiple cooling states, such as by providing a controllercoupled with the needle lumen via a valve. The controller might, forexample, have a first configuration for providing an initial coolingstate and a second configuration for providing a treatment temperaturein a target range. The treatment temperature might be established bygenerating a target treatment pressure in the lumen, while the initialcooling state could be configured (for example) to induce gradualcooling of the needle using an intermediate treatment pressure in theneedle lumen that is higher than the target treatment pressure.

A variety of refinements may be included to increase the efficiencyand/or efficacy of the system. For example, while many embodiments mayemploy needles having circular cross-sections, an outer surface of theneedle may optionally have an elongate cross-section to promote coolingof a greater volume of the target tissue. In some embodiments, aproximal cross-section of the needle might be circular to limit coolingadjacent the skin, with the elongate cross-section comprising anelliptical cross-section to enhance cooling along the target tissue. Thedistal end of such a needle might have a sharpened cutting edge. Thecooling fluid may, when vaporizing within the needle lumen, cool anouter surface of the needle to a temperature in a treatment temperaturerange substantially throughout an entire insertable length of the needleextending from the distal end of the needle to the proximal end of theneedle, such that a target tissue extending to the skin surface can betreated.

In another aspect, the invention provides a method for treating a targettissue of a patient. The method comprises advancing a needle distally topenetrate into the target tissue, the needle having a lumen and a lessthan 16 gauge needle size. A cooling fluid flow is directed distallywithin the target tissue through a supply lumen within the needle. Thetarget tissue is cooled by vaporizing a liquid from the cooling flowwithin the needle lumen.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of a self-contained subdermal cryogenicremodeling probe and system, according to an embodiment of theinvention.

FIG. 1B is a partially transparent perspective view of theself-contained probe of FIG. 1A, showing internal components of thecryogenic remodeling system and schematically illustrating replacementtreatment needles 15 for use with the disposable probe.

FIG. 2 schematically illustrates components that may be included in thetreatment system.

FIG. 3 is a schematic cross-sectional view of an embodiment of a distalportion of the probe and system of FIG. 1B, showing a replaceable needleand an pressure relief valve with a limited exhaust volume.

FIG. 3A illustrates an exemplary fused silica cooling fluid supply tubefor use in the replaceable needle of FIG. 3.

FIG. 4 is a more detailed view of a replaceable needle assembly for usein the system of FIGS. 1A and 1B.

FIGS. 5A-5C illustrate an exemplary supply valve for use in the probeand system of FIGS. 1A and 1B.

FIGS. 6A-6C, 7 and 8 illustrate skin-engaging surfaces that selectablylimit an effective insertable length of the needle, that applypain-dulling pressure, and that apply inflammation-inhibiting cooling tothe skin before and/or during treatment of the target tissue,respectively.

FIGS. 9, 9A, and 9B schematically illustrate a needle having an elongatecross-section to enhance the volume of treated tissue.

FIG. 10 schematically illustrates a thermal model of a cryogenicmicroprobe needle.

FIGS. 10A-10C graphically illustrate aspects of cryogenic cooling usingnitrous oxide in the microprobe needles described herein.

FIGS. 11A and 11B schematically illustrate cross-sectional views coolingwith a one needle system and a multiple needle system.

FIG. 12 graphically illustrates non-uniform cooling that can result frominadequate evaporation space within a small cryogenic needle probe.

FIGS. 13A-13D graphically illustrate effects of changes in exhaustvolume on the cooling response by a small cryogenic needle probe.

FIG. 14 schematically illustrates a cryogenic microprobe needle systembeing used for a dermatological treatment.

FIG. 15 is a flow chart schematically illustrating a method fortreatment using the disposable cryogenic probe and system of FIG. 1B.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides improved medical devices, system, andmethods. Embodiments of the invention will facilitate remodeling oftissues disposed at and below the skin, optionally to treat a cosmeticdefect, a lesion, a disease state, and/or so as to alter a shape of theoverlying skin surface.

Among the most immediate applications of the present invention may bethe amelioration of lines and wrinkles, particularly by inhibitingmuscular contractions which are associated with these cosmetic defectsso as so improve an appearance of the patient. Rather than relyingentirely on a pharmacological toxin or the like to disable muscles so asto induce temporary paralysis, many embodiments of the invention will atleast in part employ cold to immobilize muscles. Advantageously, nerves,muscles, and associated tissues may be temporarily immobilized usingmoderately cold temperatures of 10° C. to −5° C. without permanentlydisabling the tissue structures. Using an approach similar to thatemployed for identifying structures associated with atrial fibrillation,a needle probe or other treatment device can be used to identify atarget tissue structure in a diagnostic mode with these moderatetemperatures, and the same probe (or a different probe) can also be usedto provide a longer term or permanent treatment, optionally by ablatingthe target tissue zone and/or inducing apoptosis at temperatures fromabout −5° C. to about −50° C. In some embodiments, apoptosis may beinduced using treatment temperatures from about −1° C. to about −15° C.,optionally so as to provide a permanent treatment that limits or avoidsinflammation and mobilization of skeletal muscle satellite repair cells.Hence, the duration of the treatment efficacy of such subdermalcryogenic treatments may be selected and controlled, with coldertemperatures, longer treatment times, and/or larger volumes or selectedpatterns of target tissue determining the longevity of the treatment.Additional description of cryogenic cooling for treatment of cosmeticand other defects may be found in co-pending U.S. patent applicationSer. No. 11/295,204 filed on Dec. 5, 2005 (now U.S. Pat. No. 7,713,266)and entitled “Subdermal Cryogenic Remodeling of Muscles, Nerves,Connective Tissue, and/or Adipose Tissue (Fat),” the full disclosure ofwhich is incorporated herein by reference.

In addition to cosmetic treatments of lines, wrinkles, and the like,embodiments of the invention may also find applications for treatmentsof subdermal adipose tissues, benign, pre-malignant lesions, malignantlesions, acne and a wide range of other dermatological conditions(including dermatological conditions for which cryogenic treatments havebeen proposed and additional dermatological conditions), and the like.Embodiments of the invention may also find applications for alleviationof pain, including those associated with muscle spasms. Hence, a varietyof embodiments may be provided.

Referring now to FIGS. 1A and 1B, a system for cryogenic remodeling herecomprises a self-contained probe handpiece generally having a proximalend 12 and a distal end 14. A handpiece body or housing 16 has a sizeand shape suitable for supporting in a hand of a surgeon or other systemoperator. As can be seen most clearly in FIG. 1B, a cryogenic coolingfluid supply 18 and electrical power source 20 are found within housing16, along with a circuit 22 having a processor for controlling coolingapplied by self-contained system 10 in response to actuation of an input24. Some embodiments may, at least in part, be manually activated, suchas through the use of a manual supply valve and/or the like, so thatprocessors, electrical power supplies, and the like may be absent.

Extending distally from distal end 14 of housing 16 is atissue-penetrating cryogenic cooling probe 26. Probe 26 is thermallycoupled to a cooling fluid path extending from cooling fluid source 18,with the exemplary probe comprising a tubular body receiving at least aportion of the cooling fluid from the cooling fluid source therein. Theexemplary probe 26 comprises a 30 g needle having a sharpened distal endthat is axially sealed. Probe 26 may have an axial length between distalend 14 of housing 16 and the distal end of the needle of between about ½mm and 5 cm, preferably having a length from about 1 cm to about 3 cm.Such needles may comprise a stainless steel tube with an inner diameterof about 0.006 inches and an outer diameter of about 0.012 inches, whilealternative probes may comprise structures having outer diameters (orother lateral cross-sectional dimensions) from about 0.006 inches toabout 0.100 inches. Generally, needle probe 26 will comprise a 16 g orsmaller size needle, typically comprising a 25 g or smaller needle.

Addressing some of the components within housing 16, the exemplarycooling fluid supply 18 comprises a cartridge containing a liquid underpressure, with the liquid preferably having a boiling temperature of theless than 37° C. When the fluid is thermally coupled to thetissue-penetrating probe 26, and the probe is positioned within thepatient so that an outer surface of the probe is adjacent to a targettissue, the heat from the target tissue evaporates at least a portion ofthe liquid and the enthalpy of vaporization cools the target tissue. Avalve (not shown) may be disposed along the cooling fluid flow pathbetween cartridge 18 and probe 26, or along the cooling fluid path afterthe probe so as to limit the temperature, time, rate of temperaturechange, or other cooling characteristics. The valve will often bepowered electrically via power source 20, per the direction of processor22, but may at least in part be manually powered. The exemplary powersource 20 comprises a rechargeable or single-use battery.

The exemplary cooling fluid supply 18 comprises a single-use cartridge.Advantageously, the cartridge and cooling fluid therein may be storedand/or used at (or even above) room temperature. The cartridges may havea frangible seal or may be refillable, with the exemplary cartridgecontaining liquid N₂O. A variety of alternative cooling fluids mightalso be used, with exemplary cooling fluids including fluorocarbonrefrigerants and/or carbon dioxide. The quantity of cooling fluidcontained by cartridge 18 will typically be sufficient to treat at leasta significant region of a patient, but will often be less thansufficient to treat two or more patients. An exemplary liquid N₂Ocartridge might contain, for example, a quantity in a range from about 7g to about 30 g of liquid.

Processor 22 will typically comprise a programmable electronicmicroprocessor embodying machine readable computer code or programminginstructions for implementing one or more of the treatment methodsdescribed herein. The microprocessor will typically include or becoupled to a memory (such as a non-volatile memory, a flash memory, aread-only memory (“ROM”), a random access memory (“RAM”), or the like)storing the computer code and data to be used thereby, and/or arecording media (including a magnetic recording media such as a harddisk, a floppy disk, or the like; or an optical recording media such asa CD or DVD) may be provided. Suitable interface devices (such asdigital-to-analog or analog-to-digital converters, or the like) andinput/output devices (such as USB or serial I/O ports, wirelesscommunication cards, graphical display cards, and the like) may also beprovided. A wide variety of commercially available or specializedprocessor structures may be used in different embodiments, and suitableprocessors may make use of a wide variety of combinations of hardwareand/or hardware/software combinations. For example, processor 22 may beintegrated on a single processor board and may run a single program ormay make use of a plurality of boards running a number of differentprogram modules in a wide variety of alternative distributed dataprocessing or code architectures.

Referring now to FIG. 2, the flow of cryogenic cooling fluid from fluidsupply 18 is controlled by a supply valve 32. Supply valve may comprisean electrically actuated solenoid valve or the like operating inresponse to control signals from controller 22, and/or may comprise amanual valve. Exemplary supply valves may comprise structures suitablefor on/off valve operation, and may provide venting of the cooling fluidpath downstream of the valve when cooling flow is halted so as to limitresidual cryogenic fluid vaporization and cooling. More complex flowmodulating valve structures might also be used in other embodiments.

The cooling fluid from valve 32 flows through a lumen 34 of a coolingfluid supply tube 36. Supply tube 36 is, at least in part, disposedwithin a lumen 38 of needle 26, with the supply tube extending distallyfrom a proximal end 40 of the needle toward a distal end 42. Theexemplary supply tube 36 comprises a fused silica tubular structure 36 ahaving a polymer coating 36 b (see FIG. 3A) and extends in cantileverinto the needle lumen 38. Supply tube 36 may have an inner lumen with aneffective inner diameter 36 c of less than about 200 μm, the innerdiameter often being less than about 100 μm, and typically being lessthan about 40 μm. Exemplary embodiments of supply tube 36 have innerlumens of between about 15 and 50 μm, such as about 30 μm. An outerdiameter or size 36 d of supply tube 36 will typically be less thanabout 1000 μm, often being less than about 800 μm, with exemplaryembodiments being between about 60 and 150 μm, such as about 90 μm or105 μm. The tolerance of the inner lumen diameter of supply tubing 36will preferably be relatively tight, typically being about +/−10 μm ortighter, often being +/−5 μm or tighter, and ideally being +/−3 μm ortighter, as the small diameter supply tube may provide the majority of(or even substantially all of) the metering of the cooling fluid flowinto needle 26.

Though supply tubes 36 having outer jackets of polyimide (or othersuitable polymer materials) may bend within the surrounding needle lumen38, the supply tube should have sufficient strength to avoid collapsingor excessive blow back during injection of cooling fluid into theneedle. Polyimide coatings may also provide durability during assemblyand use, and the fused silica/polymer structures can handle pressures ofup to 100 kpsi. The relatively thin tubing wall and small outer size ofthe preferred supply tubes allows adequate space for vaporization of thenitrous oxide or other cooling fluid within the annular space betweenthe supply tube 36 and surrounding needle lumen 38. Inadequate space forvaporization might otherwise cause a buildup of liquid in that annularspace and inconsistent temperatures, as illustrated in FIG. 12.Exemplary structures for use as supply tube 36 may include the flexiblefused silica capillary tubing sold commercially by PolymicroTechnologies, LLC of Phoenix, Ariz. under model names TSP, TSG, and TSU,optionally including model numbers TSP 020090, TSP040105, and/or others.

Referring now to FIGS. 2 and 3, the cooling fluid injected into lumen 38of needle 26 will typically comprises liquid, though some gas may alsobe injected. At least some of the liquid vaporizes within needle 26, andthe enthalpy of vaporization cools the tissue engaged by the needle.Controlling a pressure of the gas/liquid mixture within needle 26substantially controls the temperature within lumen 38, and hence thetreatment temperature range of the tissue. A relatively simplemechanical pressure relief valve 46 may be used to control the pressurewithin the lumen of the needle, with the exemplary valve comprising avalve body 48 (here in the form of a ball bearing) urged against a valveseat 50 by a biasing spring 52.

During initiation of a cooling cycle, a large volume along the coolingfluid pathway between the exit from the supply tube and exit from thepressure relief valve 46 may cause excessive transients. In particular,a large volume in this area may result in initial temperatures that aresignificantly colder than a target and/or steady state temperature, ascan be seen in FIG. 13D. This can be problematic, particularly when (forexample) the target temperature is only slightly warmer than anundesirable effect inducing temperature, such as when remodeling throughapoptosis or the like while seeking to inhibit necrosis. To limit suchtransients, the pressure relief valve 46 may be integrated into ahousing 54 supporting needle 26, with the valve spring 52 being locatedoutside the valve seat (and hence the pressure-control exit frompressure relief valve 46). Additionally, where needle 26 is included ina replaceable needle assembly 26A, pressure relief valve 46 is alsolocated adjacent the interface between the needle assembly and probehandpiece housing 54. A detent 56 may be engaged by a spring supportedcatch to hold the needle assembly releasably in position, and thecomponents of the needle assembly 26A (such as a brass or other metallichousing, a polyimide tubing 58, needle 26, and the like) may be affixedtogether using adhesive. Alternatively, as illustrated in FIGS. 1B and4, the needle assembly and handpiece housing may have correspondingthreads for mounting and replacement of the needle assembly. O-rings 60can seal the cooling fluid pathway.

FIGS. 13A-13C present additional details on the effects of exhaustvolume on cooling transients. In each case, a graph of temperature overtime is shown for the outside temperature of an in vivo 30 g coolingneedle with a target temperature of about −12° C. The devices wereconstructed with different exhaust volumes, with the volume beinggreater than about 0.009 in³ in the embodiment of FIG. 13A. Theembodiment of FIGS. 13B and 13C had exhaust volumes of about 0.009 in³and about 0.0025 in³, respectively. The data collection rate was about0.7 sec for the embodiment of FIG. 13A, while the embodiments of FIGS.13B and 13C both had data collection rates of about 0.1 sec, so that theactual nadir for the embodiment of FIG. 13A may have actually beensignificantly lower than that shown. Regardless, the exhaust volume ispreferably less than about 0.05 in³, typically being less than 0.01 in³and/or 0.009 in³, and ideally being less than 0.005 in³.

Alternative methods to inhibit excessively low transient temperatures atthe beginning of a refrigeration cycle might be employed instead of ortogether with the limiting of the exhaust volume. For example, thesupply valve might be cycled on and off, typically by controller 22,with a timing sequence that would limit the cooling fluid flowing sothat only vaporized gas reached the needle lumen (or a sufficientlylimited amount of liquid to avoid excessive dropping of the needle lumentemperature). This cycling might be ended once the exhaust volumepressure was sufficient so that the refrigeration temperature would bewithin desired limits during steady state flow.

Additional aspects of the exemplary supply valves 32 can be understoodwith reference to FIGS. 2, 3, and 5A-5C. In FIG. 3, the valve is shownin the “on” configuration, with O-rings 60 sealing either side of thecooling fluid flow path and the cooling fluid flowing around the movablevalve member. In FIGS. 5A-5C, the cooling fluid flows through a passage64 that extends axially along an alternative valve body of valve body32′ when the valve is in the on configuration (seen in FIG. 5B), withthe O-rings being disposed between recesses in the movable valve body soas to allow the valve to operate when the valve body is in anyrotational orientation about its axis. In both embodiments, the coolingfluid flow path downstream of the valve is vented when the valve is inthe “off” configuration (in the embodiment of FIG. 3, by channel 66, andin the embodiment of FIGS. 5A-5C by the vaporizing cooling fluid flowingthrough the annular space between the valve body and the adjacenthousing 54 so as to preserve the cooling fluid within the movable valvebody).

Venting of the cooling fluid from the cooling fluid supply tube 36 whenthe cooling fluid flow is halted by supply valve 32, 32′ is advantageousto provide a rapid halt to the cooling of needle 26. For example, a 2.5cm long 30 g needle cooled to an outside temperature of −15° C. mightuse only about 0.003 g/sec of nitrous oxide after the system approachesor reaches steady state (for example, 10 seconds after initiation ofcooling). If the total volume along the cooling fluid path from supplyvalve to the distal end or release port of supply tube 36 is about 0.1cc, the minim time to flow all the vaporizing liquid through the supplytube might be calculated as follows:

0.1 cc (0.7 g/cc)=0.07 g of liquid nitrous oxide,

0.07 g/(0.003 g/sec)=23 sec.

These calculation assume a fused silica supply tube sized to allow theminimum flow of nitrous oxide when fluid supply has a pressure of about900 psi. When the supply valve is shut off, the pressure on the needleside of the supply valve would decay, causing the actual residual runtime to be longer, with only a partial cooling near the distal tip ofneedle 16. Regardless, it is desirable to limit the flow of coolingfluid into the needle to or near that which will vaporize in the needleso as to facilitate use of a simple disposable cooling fluid supplycartridge 18. Analytical models that may be used to derive these coolingflows include that illustrated in FIG. 10, which may be combined withthe properties of the cooling fluid (such as the pressure/enthalpydiagram of nitrous oxide seen in FIG. 10A) and the thermal properties oftissue shown in Table I to determine theoretical minimum cooling fluidflow rates (see FIG. 10B), theoretical minimum cooling fluid quantities(see FIG. 10C), and the like.

TABLE 1 Property Units Value Upper temperature bond of freezing (T₂) °C. −1 Peak of phase transition temperature (T₃) ° C. −3 LowerTemperature bond of freezing (T₁) ° C. −8 Thermal conductivity inunfrozen region (k₀) W/(mm-° C.) 0.00063 Thermal conductivity in frozenregion (k_(f)) W/mm-° C.) 0.00151 Volumetric specific heat in unfrozenregion J/mm³-° C.) 0.00316 ({ρ_(t)c_(t}f)) Volumetric specific heat infrozen region J/mm³-° C. 0.00193 ({ρ_(t)c_(t}f)) Latent heat ofsolidification (HF) J/mm³ 0.300

Referring now to FIGS. 3 and 4, a wide variety of alternativeembodiments and refinements may be provided. Fluid supply 18 may beinitially opened for use by penetrating a frangible seal of thecartridge with a pierce point 70 (such as by tightening a threadedcartridge support coupled to housing 54), with the nitrous beingfiltered by a filter 72 before being transmitted further along thecooling fluid path. Suitable filters may have pore sizes of from about 6to about 25 μm, and may be available commercially from Porex of Georgia(or a variety of alternative suppliers), or may comprise a finestainless steel screen (such as those having a mesh size of 635 with0.0009″ wire and spacing between the wire edges of approximately0.0006″), or the like. A wide variety of epoxy or other adhesives 74 maybe used, and the replaceable needle housing 24A and other structuralcomponents may comprise a wide variety of metals or polymers, includingbrass or the like. Fins 76 may be included to help vaporize excesscooling liquid traveling proximally of the insertable length of needle26.

Very fine needles will typically be used to deliver to cooling at and/orbelow the surface of the skin. These needles can be damaged relativelyeasily if they strike a bone, or may otherwise be damaged or deformedbefore or during use. Fine needles well help inhibit damage to the skinduring insertion, but may not be suitable for repeated insertion fortreatment of numerous treatment sites or lesions of a particularpatient, or for sequential treatment of a large area of the patient.Hence, the structures shown in FIGS. 1B, 3, and 4 allow the use probebodies 16, 54 with a plurality of sequentially replaceable needles.O-rings 60 help to isolate the cooling fluid supply flow (which may beat pressures of up to about 900 psi) from the exhaust gas (which may beat a controlled pressure in a range between about 50 and 400 psi,depending on the desired temperature). Exemplary O-rings may comprisehydrogenated Buna-N O-rings, or the like.

It may be advantageous to increase the volume of tissue treated by asingle treatment cycle. As it is often desirable to avoid increasing theneedle size excessively, along with selecting needles of differentlengths, needle assemblies having differing numbers of needles in aneedle array may also be selected and mounted to the probe body. Otherembodiments may employ a single needle array fixedly mounted to theprobe body, or a plurality of replaceable needle assemblies which allinclude the same number of needles. Regardless, cooling fluid flow to aplurality of needles may be provided, for example, by inserting andbonding a plurality of fused silica supply tubes into a 0.010 polyimidetubing 58 or header within the needle assembly, and by advancing thedistal end of each supply tube into a lumen of an associated needle 26.The needles might vent into a common exhaust space coaxially aroundpolyimide tubing 58 in a manner similar to the single needle designshown. This can increase the quantity of tissue treated adjacent and/orbetween needles, as can be seen by comparing the theoretical 15 secondexposures to one and two needles having a −15° C. probe surface, asshown in FIGS. 11A and 11B, respectively.

Referring now to FIGS. 6A-6C, it may be desirable to allow a system userto select a treatment depth, and/or to treat the skin surface to atemperature similar to that of the underlying target tissue along needle26. A distally oriented surface 82 supported by probe body 54 adjacentand/or around the proximal end of the needles may be configured to limitheat transfer to or from the skin when the needle 26 is inserted so thatsurface 82 engages the skin and cooling fluid flows into the needle.Exemplary heat transfer limiting surfaces may be formed, for example,from a small rigid foam pad or body 84. Closed cell polyethylene foam orStyrofoam™ foam bodies may be used. As seen in FIG. 6A-6C, analternatively selectable set of bodies may also have differingthicknesses between the skin engaging-surface 82 and a surface 86 thatengages the distal portion of the probe body. A user can then select aninsertable length of the needle by selecting an appropriate probe body84, 84 a, 84 b and mounting the selected probe body onto the needles.Skin engaging surface 82 of bodies 84, 84 a, and 84 b (or some otherskin engaging surface adjacent the distal end of the needle) may be usedto apply pressure to the skin, lesion, and/or target tissue duringtreatment. Alternative intertable length varying arrangements may alsobe provided, including those having threaded or other articulatablestructures supporting the skin engaging surface 82 relative to theadjacent probe body 54 and the like.

Referring now to FIG. 7, the application of pressure before, during,and/or after cooling may help dull or otherwise inhibit sharp pain. Suchpain may otherwise result from the skin penetration, cooling, or thawingof the target and/or collateral tissues. It may also be beneficial toobscure the patient's view of the cooling needles, and/or to cover theneedles when not in use so as to inhibit needle-stick injuries andpotential disease transmission. Toward that end, skin-engaging surface82 may be supported by an articulatable support structure having a firstconfiguration (shown in solid in FIG. 7) and a second configuration(shown dashed in FIG. 7). A simple spring mechanism may be used to applya desired contact force between the skin-engaging surface 82 and thepatient before insertion and during cooling. More sophisticatedarrangements can also be employed in which the needle is driven distallyand then proximally relative to the skin engaging surface appropriatetimes after sufficient pressure is applied to the patient, and the like.

Referring now to FIG. 8, still further alternative embodiments may beprovided, in this case to apply different cooling temperatures to thepatient, and/or to apply cooling to the skin surface and to a targettissue adjacent needle 26. For example, in the case of acne it may bedesirable to have two different cooling target temperatures, withcooling on the skin surface to inhibit inflammation (such as to about−10° C.), and (see FIG. 14) cooling of a target tissue TT cylinderaround needle 26 sufficient to kill bacteria in the sebaceous gland andenlarged follicle opening (such as to about −20° C.). This dualtemperature treatment may be particularly beneficial for severe forms ofacne involving cysts or nodules. To provide cooling of tissue engagingsurface 82, that surface may be thermally coupled to a chamber 88.Cooling fluid may be transmitted into chamber 88 by a port of a coolingfluid supply tube 36, and the pressure of chamber 88 (and hence thetemperature within the chamber) can optionally be controlled by adedicated additional pressure relief valve 46 a. As the pressure withinchamber 88 may differ from that within the needle, different treatmenttemperatures may be provided. The structures described herein can alsobe combined, for example, with the dual skin surface/needle temperaturetreatment structure of FIG. 8 being compatible with the replaceableneedle systems of FIGS. 1B, 3, and/or 4. The dual skin surface/needletreatment systems and methods may also be compatible, for example, withthe articulatable skin surface supports of FIG. 7 so as to apply cooledpressure to the skin prior to and/or during needle insertion using aflexible fluid supply tube or the like.

Still further alternatives may also be provided, including systems thatgenerate a high rate of cooling to promote necrosis of malignant lesionsor the like. High cooling rates limit osmotic effects in the targettissue. Slow cooling may tend to promote ice formation between cellsrather than within cells due to the osmotic effect. While such slowcooling can be provided where necrosis is not desired (such as throughthe use of a proportion supply valve to modulate flow, a processorgenerated on/off cycle during initial cooling, or the like), the needleprobes described herein will often be well suited to induce rapidcooling rates of the target tissue by vaporizing the cooling fluid inclose thermal and spatial proximity to that target tissue. Hence, wherenecrosis of cells by intracellular ice formation is desired, coolingrates of about 25° C./sec or more, or even about 50° C./sec or more canbe provided.

Referring now to FIGS. 9, 9A, and 9B, needles having circularcross-sectional shapes can often be used, but may not always provide thedesired surface area for the cross-sectional area of the needle.Increased surface area may decrease the amount of time the needle isinserted to cool a volume of tissue to a temperature in a target range.Hence, a needle with an elongate outer cross-section such as ellipticalneedle 90 may be desirable. A distal cutting edge 92 at the distal tipmay facilitate insertion and a circular cross-section 94 near theproximal end may limit cooling adjacent the skin, while cooling of thetarget tissue therebetween is enhanced by elliptical cross-section 96.

Referring now to FIG. 15, a method 100 facilitates treating a patientusing a cryogenic cooling system having a self-contained disposablehandpiece and replaceable needles such as those of FIG. 1B. Method 100generally begins with a determination 110 of the desired tissueremodeling and results, such as the alleviation of specific cosmeticwrinkles of the face, the inhibition of pain from a particular site, thealleviation of unsightly skin lesions or cosmetic defects from a regionof the face, or the like. Appropriate target tissues for treatment areidentified 112 (such as the subdermal muscles that induce the wrinkles,a tissue that transmits the pain signal, or the lesion-inducing infectedtissues), allowing a target treatment depth, target treatmenttemperature profile, or the like to be determined 114. An appropriateneedle assembly can then be mounted 116 to the handpiece, with theneedle assembly optionally having a needle length, skin surface coolingchamber, needle array, and/or other components suitable for treatment ofthe target tissues. Simpler systems may include only a single needletype, and/or a first needle assembly mounted to the handpiece.

As described above, pressure, cooling, or both may be applied 118 to theskin surface adjacent the needle insertion site before, during, and/orafter insertion 120 and cryogenic cooling 122 of the needle andassociated target tissue. The needle can then be retracted 124 from thetarget tissue. If the treatment is not complete 126 and the needle isnot yet dull 128, pressure and/or cooling can be applied to the nextneedle insertion location site 118, and the additional target tissuetreated. However, as small gauge needles may dull after being insertedonly a few times into the skin, any needles that are dulled (orotherwise determined to be sufficiently used to warrant replacement,regardless of whether it is after a single insertion, 5 insertions, orthe like) during the treatment may be replaced with a new needle 116before the next application of pressure/cooling 118, needle insertion120, and/or the like. Once the target tissues have been completelytreated, or once the cooling supply cartridge included in theself-contained handpiece is depleted, the used handpiece and needles canbe disposed of 130.

A variety of target treatment temperatures, times, and cycles may beapplied to differing target tissues to as to achieve the desiredremodeling. For example, (as more fully described in patent applicationSer. No. 11/295,204, previously incorporated herein by reference)desired temperature ranges to temporarily and/or permanently disablemuscle, as well as protect the skin and surrounding tissues, may beindicated by Table II as follows:

TABLE II Temperature Skin Muscle/Fat   37° C. baseline baseline   25° C.cold sensation   18° C. reflex vasodilation of deep blood vessels   15°C. cold pain sensation   12° C. reduction of spasticity   10° C. verycold sensation reduction of chronic oedema Hunting response  5° C. painsensation  0° C. freezing point  −1° C. Phase transition begins  −2° C.minimal apoptosis  −3° C. Peak phase transition  −5° C. tissue damagemoderate apoptosis  −8° C. Completion of phase transition −10° C.considerable apoptosis −15° C. extensive apoptosis mild-moderatenecrosis −40° C. extensive necrosis

To provide tissue remodeling with a desired or selected efficacyduration, tissue treatment temperatures may be employed per Table III asfollows:

TABLE III Cooled Temperature Range Time Effectiveness Purpose ≥0° C.Treatment lasts only while the Can be used to identify target needle isinserted into the tissues. target tissue. From 0° C. to −5° C. Oftenlasts days or weeks, and Temporary treatment. Can be target tissue canrepair itself. used to evaluate effectiveness Embodiments may last hoursof remodeling treatment on or days. skin surface shape or the like. From−5° C. to −15° C. Oftern last months to years; Long term, potentiallyand may be permanent. permanent cosmetic benefits. Limited musclerepair. Can be deployed in limited Embodiments may last weeks doses overto time to achieve to months. staged impact, controlling outcome andavoiding negative outcome. May be employed as the standard treatment.From −15° C. to −25° C. Often lasts weeks or months. May result inMid-term Muscle may repair itself via cosmetic benefits, and can besatellite cell mobilization. used where permanent effects Embodimentsmay last years. are not desired or to evaluate outcomes of potentiallypermanent dosing. Embodiments may provide permanent treatment.

There is a window of temperatures where apoptosis can be induced. Anapoptotic effect may be temporary, long-term (lasting at least weeks,months, or years) or even permanent. While necrotic effects may be longterm or even permanent, apoptosis may actually provide more long-lastingcosmetic benefits than necrosis. Apoptosis may exhibit anon-inflammatory cell death. Without inflammation, normal muscularhealing processes may be inhibited. Following many muscular injuries(including many injuries involving necrosis), skeletal muscle satellitecells may be mobilized by inflammation. Without inflammation, suchmobilization may be limited or avoided. Apoptotic cell death may reducemuscle mass and/or may interrupt the collagen and elastin connectivechain. Temperature ranges that generate a mixture of these apoptosis andnecrosis may also provide long-lasting or permanent benefits. For thereduction of adipose tissue, a permanent effect may be advantageous.Surprisingly, both apoptosis and necrosis may produce long-term or evenpermanent results in adipose tissues, since fat cells regeneratedifferently than muscle cells.

While the exemplary embodiments have been described in some detail forclarity of understanding and by way of example, a number ofmodifications, changes, and adaptations may be implemented and/or willbe obvious to those as skilled in the art. For example, one or moretemperature feedback loops may be used to control the treatments, withthe tissue temperature optionally being taken using a temperaturesensing needle having a temperature sensor disposed adjacent an outercooled skin engaging surface of the needle. Hence, the scope of thepresent invention is limited solely by the independent claims.

What is claimed is:
 1. A system for treating a nerve associated with atarget tissue of a patient, the system comprising: a needle having aproximal end, a distal end, and a lumen therebetween, the needlecomprising a 16 gauge or smaller needle size; a cooling fluid supplylumen extending distally within the needle; and a cooling fluid sourcecoupleable to the supply lumen to direct cooling fluid flow into theneedle lumen so that liquid from the cooling fluid flow vaporizes withinthe target tissue when the needle extends into the target tissue so asto cryogenically treat the nerve; wherein the supply lumen is defined bya non-metallic tubular supply tube having an outer diameter less than800 μm.
 2. The system of claim 1, wherein the needle comprises a 25gauge or smaller needle size, and has a tip suitable for penetrating askin surface.
 3. The system of claim 2, wherein the supply lumen isdefined by a supply tube comprising fused silica, wherein the supplytube further has a polymer coating over the fused silica.
 4. The systemof claim 3, wherein the supply tube extends in cantilever distally intothe needle lumen, and wherein the supply tube has sufficient stiffnessto inhibit flow induced buckling of the supply tube within the needlelumen.
 5. The system of claim 2, wherein the supply lumen has an innerdiameter of less than 100 μm.
 6. The system of claim 2, wherein anaspect ratio defined by an insertable length of the needle to an outersize of the needle is more than
 20. 7. The system of claim 2, furthercomprising a handle supporting the needle, the supply lumen, and thefluid source for manual manipulation during treatment.
 8. The system ofclaim 2, further comprising a pressure relief valve in fluidcommunication with the needle lumen so as to control a pressure of thevaporizing cooling fluid flow within the needle such that a temperatureof the target tissue is within a desired treatment temperature range. 9.The system of claim 8, wherein an exhaust volume is between the supplylumen and the pressure relief valve and is less than about 0.05 in³. 10.The system of claim 8, wherein the cooling fluid flow is meteredprimarily by a flow resistance of the supply lumen, and the metered flowinhibits temperature fluctuation by maintaining a liquid/gas mixturewithin the needle lumen.
 11. The system of claim 8, wherein the coolingfluid flow is not actively modulated between the fluid source and theneedle lumen during cooling, wherein the pressure relief valve comprisesa biasing spring mechanically urging a valve member against a valve seatso as to maintain pressure within the needle lumen within a desiredpressure range, and wherein the biasing spring is disposed outside anexhaust volume extending from the supply lumen to the valve seat. 12.The system of claim 2, further comprising a supply valve disposedbetween the supply lumen and the fluid source, the system having acooling fluid supply volume between the needle lumen and the supplyvalve, the valve having a first configuration and a secondconfiguration, the valve in the first configuration providing fluidcommunication between the fluid source and the supply volume, the valvein the second configuration inhibiting the cooling flow and venting thesupply volume so as to limit cooling fluid vaporization within theneedle lumen after the valve moves from the first configuration to thesecond configuration.
 13. The system of claim 1, further comprising: ahandpiece body supporting the needle; and at least one distally orientedskin engaging surface supported by the handpiece body so as to engagethe skin surface before, during and/or after cryogenically treating thenerve to warm the skin surface.
 14. The system of claim 1, wherein, whenthe cooling fluid flow is initiated, an outer surface of the needleengaging the target tissue cools at a rate of more than about 25° C./secso as to promote intracellular ice formation and necrosis of the nerve.15. The system of claim 1, further comprising an array of needlescoupled to the fluid source, each needle, when the cooling fluid flow isinitiated, having an outer surface that cools at a rate of more thanabout 25° C./sec so as to promote intracellular ice formation andnecrosis of the target tissue between the needles.
 16. The system ofclaim 1, wherein the cooling fluid fluid, when vaporizing within theneedle lumen cools an outer surface of the needle to a temperature in atreatment temperature range throughout an insertable length of theneedle between the distal end and the proximal end such that the nervecan be treated.
 17. The system of claim 1, further comprising: a secondneedle having a proximal end, a distal end, and a second needle lumentherebetween, the second needle comprising a 16 gauge or smaller needlesize; a second cooling fluid supply partially disposed within the secondneedle lumen, the second cooling fluid supply comprising a fused silicatube having a polymer coating, and wherein the cooling fluid source iscoupleable to the second cooling fluid supply to direct cooling fluidflow into the second needle lumen so as to cryogenically treat thenerve.
 18. The system of claim 17, further comprising a single tubingstructure coupled to the cooling fluid source and the cooling fluidsupply tubes.
 19. The system of claim 1, wherein cryogenically treatingthe nerve comprises alleviating pain of the patient associated with thenerve.